Analysis of clinicopathological features and NAB2-STAT6 fusion variants of meningeal solitary fibrous tumor with ectopic salivary gland components in the cerebellopontine angle.

Solitary fibrous tumors (SFTs) are rare mesenchymal tumors that can occur at any location. Since the identification of specific NAB2-STAT6 fusion in SFTs, the fusion gene variants, NAB2 exon 4-STAT6 exon 2/3 and NAB2 exon 5/6/7-STAT6 exon 16/17/18, have been reported to be associated with clinicopathological features, and the latter variant is predominant in meningeal SFTs. SFTs developing in the salivary glands are rare, and more rarely, those involving ectopic salivary glands (ESGs) have been reported in the cerebellopontine angle (CPA); however, their characteristics remain not well understood. In this study, we performed a clinicopathological and molecular analysis of 3 cases of meningeal SFT with ESGs. All cases presented with an extra-axial mass in the CPA, which is a rarer location for intracranial ESGs compared to the sellar region. Histologically, except for the presence of ESGs, there was no significant difference between current cases and ordinary SFTs. The ESGs demonstrated no cellular atypia, and although the spindle tumor cells were immunopositive for STAT6, the ESGs were negative in all cases, supporting that the ESGs are non-neoplastic components. In 1 case, ESGs were found only in the primary tumor and disappeared in recurrence/dissemination. Of note, molecular analysis identified NAB2 exon 4-STAT6 exon 2 in all cases. In conclusion, our results suggest that ESGs particularly in the CPA may be associated with SFTs and that meningeal SFTs with ESGs may be associated with the minor fusion variant of NAB2-STAT6 in the intracranial lesions.

A cerebellopontine angle mouse model for the investigation of tumor biology, hearing, and neurological function in NF2-related vestibular schwannoma.

Neurofibromatosis type II (NF2) is a disease that lacks effective therapies. NF2 is characterized by bilateral vestibular schwannomas (VSs) that cause progressive and debilitating hearing loss, leading to social isolation and increased rates of depression. A major limitation in NF2 basic and translational research is the lack of animal models that allow the full spectrum of research into the biology and molecular mechanisms of NF2 tumor progression, as well as the effects on neurological function. In this protocol, we describe how to inject schwannoma cells into the mouse brain cerebellopontine angle (CPA) region. We also describe how to apply state-of-the-art intravital imaging and hearing assessment techniques to study tumor growth and hearing loss. In addition, ataxia, angiogenesis, and tumor-stroma interaction assays can be applied, and the model can be used to test the efficacy of novel therapeutic approaches. By studying the disease from every angle, this model offers the potential to unravel the basic biological underpinnings of NF2 and to develop novel therapeutics to control this devastating disease. Our protocol can be adapted to study other diseases within the CPA, including meningiomas, lipomas, vascular malformations, hemangiomas, epidermoid cysts, cerebellar astrocytomas, and metastatic lesions. The entire surgical procedure takes ~45 min per mouse and allows for subsequent longitudinal imaging, as well as neurological and hearing assessment, for up to 2 months.

Pantopaque contrast mimicking intracanalicular vestibular schwannoma.

Pantopaque (iophendylate) is an oily contrast medium historically used during spine imaging. Due to its persistence in the subarachnoid space and the potential to lead to severe arachnoiditis, it is no longer used today. We present a 40-year-old male with new-onset headaches, imbalance, and vertigo. Brain magnetic resonance imaging revealed a 2-mm T1 -hyperintense intracanalicular lesion. Numerous hyperdense foci were scattered throughout the subarachnoid space on computed tomography. Further history revealed the patient received Pantopaque 30 years prior, after sustaining spinal trauma. Remnant Pantopaque contrast is an important differential when evaluating a patient with a suspected intracranial tumor in order to avoid unwarranted surgical intervention. Laryngoscope, 127:1916-1919, 2017.

Myoepithelioma of the cerebellopontine angle: a previously not documented benign salivary gland-type neoplasm within the cranium.

Myoepithelioma is a dimorphic neoplasm with contractile-epithelial phenotype, originally interpreted as deriving from, but not actually restricted to the salivary glands. As a novel addition to the list of exquisitely rare intracranial salivary gland-type tumors and tumor-like lesions, we report on an example of myoepithelioma encountered in the left cerebellopontine angle of a 32-year-old male. Clinically presenting with ataxia and dizziness, this extraaxial mass of 4 × 3.5 × 3 cm was surgically resected, and the patient is alive 6 years postoperatively. Histologically, the tumor exhibited a continuum ranging from compact fascicles of spindle cells to epithelial nests and trabeculae partitioned by hyalinized septa, while lacking tubular differentiation. Regardless of architectural variations, there was robust immunoexpression of S100 protein, smooth muscle actin, GFAP, cytokeratin, and vimentin. Cytologic atypia tended to be modest throughout, and the MIB1 labeling index averaged less than 1%. Fluorescent in situ hybridization indicated no rearrangement of the EWSR1 locus. We interpret these results to suggest that myoepithelioma of the posterior fossa - along with related salivary epithelial tumors in this ostensibly incongruous locale - may possibly represent analogous neoplasms to their orthotopic counterparts, ones arising within aberrant salivary anlagen. The presence of the latter lends itself to being mechanistically accounted for by either postulating placodal remnants in the wake of branchial arch development, or linking them to exocrine glandular nests within endodermal cysts. Alternatively, myoepithelioma at this site could be regarded as a non tissue-specific lesion similar to its relatives ubiquitously occurring in the soft parts.

Diagnostic value of EAAT-1 and Kir7.1 for distinguishing endolymphatic sac tumors from choroid plexus tumors.

The endolymphatic sac tumor (ELST) is a low-grade carcinoma originating in the ear. These extremely rare tumors are capable of invading the cerebellopontine angle and might be mistaken for choroid plexus tumors (CPTs) in this region. Currently, these tumors are distinguished by conventional morphologic and immunohistochemical studies for S-100, cytokeratin, and GFAP expression, but all markers are variably expressed by both tumors. Therefore, we examined new promising markers such as EAAT-1 and Kir7.1 in 4 ELSTs and 35 CPTs located in the fourth ventricle or at the cerebellopontine angle in adults. Immunohistochemical expression of Kir7.1 was found in 30 (100%) of 30 and EAAT-1 in 32 (91%) of 35 CPTs tested and was absent in all ELSTs. Expression of GFAP was found in 16 (55%) and S-100 in 29 (100%) of 29 CPTs tested, but both markers were also expressed in 2 of 4 ELSTs examined. Specificity and sensitivity of Kir7.1 (both 100%) and EAAT-1 (100% and 91%, respectively) were superior to the values for S-100 (50% and 100%, respectively) and GFAP (50% and 55%, respectively) for distinguishing CPT from ELST.

Desmoplastic small round cell tumor of the central nervous system: report of two cases and review of the literature.

Desmoplastic small round cell tumor (DSRCT) is a malignant tumor often involving the abdominal and/or pelvic peritoneum. Only one fully documented example has arisen in the central nervous system (CNS). Herein, we describe two additional examples, fulfilling the morphologic, immunohistochemical, and molecular criteria (EWS/WT1 translocation) of DSRCT. Both arose in the cerebellopontine angle (CPA) and underwent spinal dissemination. Patient 1, a 37-year-old male, underwent a subtotal resection, and 2 years later died of recurrent disease with spinal dissemination. Patient 2, a 39-year-old man, presented with cerebellar and CPA lesions as well as spinal leptomeningeal deposits. After 27 months of adjuvant therapy, he is alive with progressive disease. In conclusion, CNS DSRCT follows a similar aggressive course as do peritoneal examples. Although rare, DSRCT warrants consideration in the differential diagnosis of "malignant small blue cell tumors" of the CNS.

Adult cerebellopontine angle medulloblastoma originating in the pons mimicking focal brainstem tumor.

We herein report a rare case of cerebellopontine angle (CPA) medulloblastoma originating in the brainstem that demonstrated a very unusual clinical presentation and radiological appearances. A 25-year-old female was admitted to our hospital with a right hearing disturbance and a right facial palsy. A small non-enhanced lesion having minimal mass effect in the right CPA was identified by using a 1.5-tesla-MR system, whose size remained almost unchanged a year. The 3-tesla MR images revealed that the precise region was in the right side of the tegmentum of the lower pons to the inferior cerebellar peduncle and the flocculus. MR spectroscopic images using a 3-tesla system revealed a high ratio of choline-to-N-acetylaspartate in the region of interest in comparison to the contra-lateral side. Craniotomy and biopsy were performed. The histopathological diagnosis was medulloblastoma. The patient received craniospinal irradiation and chemotherapy, and achieved complete remission by the time of the follow-up MR images. She is now doing well with a full recovery of the right facial palsy. MR spectroscopic imaging is considered to be quite useful for the management of this rare type of brainstem tumor.

Multiple neuroenteric cysts at cerebello-pontine angle and foramen magnum: a case report and review of the literature.

Neuroenteric cysts of the CNS are uncommon benign lesions usually involving the spinal cord or rarely the cerebellopontine angle (CPA). We report a rare example of multiple neuroenteric cysts arising from the CPA and foramen magnum in a 20-year-old Caucasian woman who presented with headaches and dizziness. An MRI showed three separate lesions, not communicating with each other. The first lesion, within the left posterior lateral aspect of the CPA, demonstrated isointensity to gray matter on the fluid-attenuated inversion recovery (FLAIR) sequence. The second lesion, within the left foramen of Luschka at the level of the CPA, demonstrated hyperintensity on the T(2)-weighted sequences, intermediate to slightly hyperintense on T(1)-weighted sequence and hyperintensity on FLAIR. The third lesion, within the anterior/inferior left cerebellum at the level of the foramen magnum, followed CSF signal intensity throughout. None of the lesions demonstrated significant enhancement or bone lesions. Due to compression effect, surgery was performed. Pathologic examination revealed cystic structures lined by a single layer of non-ciliated well-differentiated mucin-producing columnar epithelium with eosinophilic to amphophilic cytoplasm and round to oval nuclei with focal pseudostratification. Immunohistochemical studies showed focal positivity for cytokeratin 7, CK 5/6, synaptophysin, and carcinoembryonic antigen (CEA), diffuse positive staining for epithelial membrane antigen (EMA) and BerEP4; and negative staining for cytokeratin 20, TTF-1, and GFAP. The MIB-1 proliferation index was < 1%. One-year follow-up has shown no recurrence. The differential diagnosis and a brief review of the literature are also presented.

Simultaneously occurring vestibular schwannoma and meningioma in the cerebellopontine angle: case report and literature review.

Simultaneously occurring multiple primary brain tumors of different histological types are rare, and the coexistence of schwannoma and meningioma in the same cerebellopontine angle (CPA) without neurofibromatosis is extremely rare. A 57-year-old female patient presented with headache, speech disturbance, left facial numbness and deafness in the left ear. Magnetic resonance imaging demonstrated two different tumors in the left CPA. These tumors were not in continuity. The tumors were totally removed through the left suboccipital approach. Histopathological examination revealed that the large tumor was a vestibular schwannoma and the smaller was a meningioma. Neurofibromatosis was not diagnosed in the patient. No recurrence was observed at the end of 9 years after the operation. The simultaneous occurrence of vestibular schwannoma and meningioma in the CPA appears coincidental. This association must be kept in mind if two different tumors are detected radiologically in the same CPA.

Cerebellopontine calcification: a new entity of idiopathic intracranial calcification?

We report the autopsy case of a 40-year-old woman with severe intellectual and motor disabilities, who showed calcification in the cerebellum and pons but not in the basal ganglia on CT scan, and died of intracranial hemorrhage due to intractable hypertension. At autopsy, numerous calcium deposits were noted in the cerebellar cortex, the dentate nucleus, the cerebellar white matter and the ventral pons. These deposits were distributed both in the neuropil and the white matter, but rarely within the arterial walls or in contact with capillaries. This weak relationship between calcification and the blood vessels, in addition to the paucity of basal ganglia calcification, is in contrast to the findings with other disorders involving intracranial calcification, including Fahr's disease and calcium metabolism disorders. Immunohistochemistry revealed intense staining of calbindin-D28K and parvalbumin at sites of calcium deposits both in the present case and in a case of pseudohypoparathyroidism, whereas these proteins were not localized to calcium deposits in the cerebellum of a Fahr's disease brain. We propose that the present case may represent a distinct entity among diseases characterized by idiopathic intracranial calcification. In addition, calcium-binding proteins may be involved in the calcification process in some cases with intracranial calcification.

Solitary fibrous tumor of the cerebellopontine angle with salivary gland heterotopia: a unique presentation.

We report the unique association of a solitary fibrous tumor of the cerebellopontine angle with ectopic salivary gland tissue in a 53-year-old woman. The patient, diagnosed 21 years earlier with a right cerebellopontine angle fibrous meningioma, presented with a recurrent mass, which, upon surgical removal, showed features of a solitary fibrous tumor. Strong and diffuse immunoreactivity to CD34 and BCL-2 and a negative epithelial membrane antigen immunostain confirmed the diagnosis. Admixed with the spindle cell neoplasm, a bland glandular element composed of small glands and variably dilated tubules was noted. The vague tubuloacinar arrangement of the glands and the presence of acinar cells with a granular, periodic acid-Schiff-positive, basophilic cytoplasm, resembling serous type acini, were features of benign, although ectopic, salivary gland tissue. The presence of a myoepithelial cell layer, surrounding some of the acini and highlighted by the smooth muscle actin immunostain, strengthened this interpretation.

Dural cerebellopontine angle metastasis from malignant parotid oncocytoma.

Malignant oncocytoma of the parotid gland is a quite rare tumor, with only 40 cases with unequivocal histological diagnosis reported in the literature. No cases with intracranial metastasis have been described. The authors report a very unusual case of malignant parotid gland oncocytoma with a large dural extracerebellar metastasis occurring in the contiguous cerebellopontine angle six months after surgery for the primary tumor. Only a partial removal of the dural metastasis was possible because of the cranial nerve and vessel encasement within the mass. Surgery and irradiation resulted in one-year survival. Interestingly, no destruction and infiltration of the petrous and temporal bones were found both at radiological and surgical exploration. We may suggest that metastatic spread from the parotid region to the cerebellopontine angle occurred through the mastoid cells or by haematogenous diffusion through the meningeal branches to the posterior fossa dura from the occipital or ascending pharyngeal arteries.

Primary extranodal marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue type in the CNS.

Extranodal marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT) type has been reported in various internal organs. Here a case is reported of MALT lymphoma developing in the cerebellopontine (CP) angle in a patient with Sjogren syndrome, and the concept of MALT lymphoma of the CNS is introduced. Pathologically, the tumor showed inflammatory features of reactive lymphocytic infiltration with follicle formation, but there were slightly atypical lymphocytes and plasmacytes with B-cell markers. These cells invaded reactive follicles, showing follicular colonization, and showed aberrant expression indicating their neoplastic nature. A review of the literature revealed eight cases of MALT lymphoma originating from the dura mater and one from the CP angle. The average age of patients was 50 years (range 28-66 years), and all patients were female. The tumors were slow to develop and the patients were cured after surgical removal and/or additional therapies. It is proposed that MALT lymphoma should be considered as a differential diagnosis of inflammatory pseudotumor of the CNS.

Pediatric acoustic schwannoma showing rapid regrowth with high proliferative activity.

Acoustic schwannoma is a slow-growing tumor and usually occurs in adult patients. We report a rare pediatric case of acoustic schwannoma with high proliferative potential. A 10-year-old boy was diagnosed as having a right cerebellopontine angle tumor. The tumor was subtotally resected. Histological examination revealed a typical acoustic schwannoma with a few mitotic figures. Chromosomal analysis showed no abnormality on the long arm of chromosome 22 associated with neurofibromatosis type 2. The lesion re-grew rapidly as an acoustic schwannoma, necessitating subtotal resection on three occasions and CyberKnife radiosurgery. The immunohistochemical MIB-1 staining indices of the specimens obtained at the first, second, and third operations were 2.3%, 4.6% and 14.7%, respectively. The immunohistochemical proliferative potential of acoustic schwannoma is discussed.